1: Mech Dev. 2000 Oct;97(1-2):141-8. 

Expression of the bZIP transcription factor TCF11 and its potential dimerization
partners during development.

Murphy P, Kolsto A.

Biotechnology Centre of Oslo, University of Oslo, P.O. Box 1125, Blindern,
N-0316, Oslo, Norway. paula.murphy@biotek.uio.no

TCF11 (also known as Nrf1 and LCR-F1) is a basic-region leucine-zipper (b-ZIP)
transcription factor that is essential during embryonic development. We have
carried out expression analysis at a number of developmental stages and find
that while there is some localized elevated expression between 8 and 9 days post
coitum (dpc), the gene is widely expressed with a constant level of mRNA
transcripts detectable in all tissues and at all stages examined. However, this
does not reflect the specific nature of a TCF11 mutant phenotype (EMBO J. 17
(1998) 1779) which shows an essential role in foetal liver haematopoiesis. The
specificity of TCF11 function may be controlled at a post-transcriptional level
including availability of, and specific interaction with, a range of potential
heterodimerization partners. We therefore carried out expression analysis of
four candidate partner molecules; the three small Maf genes and another bZIP
transcription factor found to bind to TCF11 in a two-hybrid screen, ATF4. We
show different patterns of expression for the three Maf genes during development
with MafG being widely expressed, MafK expressed only later in development and
in specific tissues, and no detection of MafF. ATF4 shows evidence of complex
regulation during development and shows elevated expression in many of the same
sites as TCF11.

PMID: 11025215 [PubMed - indexed for MEDLINE]


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2: Nucleic Acids Res. 1998 Jan 15;26(2):512-20. 

Interaction of the CNC-bZIP factor TCF11/LCR-F1/Nrf1 with MafG: binding-site
selection and regulation of transcription.

Johnsen O, Murphy P, Prydz H, Kolsto AB.

Biotechnology Centre of Oslo, University of Oslo, PO Box 1125, Blindern N-0316
Oslo, Norway.

We have previously shown that the widely expressed human transcription factor
TCF11/LCR-F1/Nrf1 interacts with small Maf proteins and binds to a subclass of
AP1-sites. Such sites are required for beta-globin 5' DNase I hypersensitive
site 2 enhancer activity, erythroid porphobilinogen deaminase inducibility,
hemin responsiveness by heme-oxygenase 1 and expression of the gene
NAD(P)H:quinone oxidoreductase1. Here we report the optimal DNA-binding
sequences for TCF11/LCR-F1/Nrf1 alone and as a heterodimer with MafG, identified
by using binding-site selection. The heterodimer recognises a 5'-TGCTgaGTCAT-3'
binding-site that is identical to the established NF-E2-site, the antioxidant
response element and the heme-responsive element while the binding specificity
of the homomer is less stringent. To investigate the activity of TCF11 through
this selected site, both alone and in the presence of MafG, we have used a
transient transfection assay. TCF11 alone activates transcription while MafG
alone acts as a repressor. When co-expressed, MafG interferes with TCF11
transactivation in a dose dependent manner. This indicates that MafG protein,
which heterodimerises efficiently with TCF11 in vitro (the heterodimer having a
higher affinity for DNA than TCF11 alone), does not co-operate with TCF11 in
transactivating transcription. We propose that since both these factors are
widely expressed, they may act together to contribute to the negative regulation
of this specific target site. Efficient positive regulation by TCF11 may require
alternative partners with perhaps more restricted expression patterns.

PMID: 9421508 [PubMed - indexed for MEDLINE]


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